Project Summary (Overall section): The UPR COBRE Center for Neuroplasticity (UPR-CCfN) was established with a COBRE phase 1 award in 2013 as a collaboration of two main UPR campuses, the Institute of Neurobiology (UPR-MSC) and the Department of Biology at UPR Rio Piedras (UPR-RP). The UPR-CCfN has since expanded collaborations to include several UPR campuses, including the Departments of Biology and Chemistry (UPRRP), Departments of Physiology, Pharmacology, Pharmacy, and Anatomy (UPR-MSC), Department of Chemistry (UPR Humacao campus), and Universidad Central del Caribe Medical School, a private institution in PR. During COBRE phases 1-2 the UPR-CCfN achieved several benchmarks: (1) It has significantly enhanced ability of new and early-stage UPR researchers to conduct competitive research in the area of neuroscience. (2) It has established a critical mass of 24 investigators. (3) It has developed the COBRE Neuroimaging and Electrophysiology Facility (NIEF) core into a state-of-the-art resource for the UPR-CCfN investigators and the larger UPR biomedical research community. This was accomplished by providing outstanding specialized technical services, training, and access to state-of- the-art instrumentation in fluorescence, confocal, and multiphoton microscopy along with electrophysiology that has enhanced the productivity of our researchers. (4) A major accomplishment of the NIEF was becoming a Nikon Center of Excellence (NCoE), globally renowned for its state-of-the- art facilities for advanced research imaging. (5) The UPR-CCfN has extraordinarily increased its biomedical research capacity as it recently took occupancy of a new state-of-the-art research infrastructure, which includes a more than $26 million institutional investment on two floors (~40 square feet) of the Molecular Science Research Center (MSRC); the Neuroplasticity Center (floor 6); and Vivarium (floor 7). (6) UPR-CCfN has developed a robust business plan that will sustain and upgrade our NIEF core facilities, provide technical support, and programmatic activities beyond COBRE Phase 3. During Phase 3 the UPR-CCfN will continue to provide a multidisciplinary cadre of investigators with cutting-edge facilities, scientific capability, and multidisciplinary collaborations with the public and biopharma sectors for the treatment of neurodegeneration-related diseases. The UPR-CCfN will foster research innovation, maximize research synergy and collaborations as well as mentoring and entrepreneurship. Our overreaching goal is that during Phase 3, the UPR-CCfN will propel into a world- recognized Center for Neuroplasticity and Neurodegeneration with translational/therapeutic applications.